Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects

Abstract

Aims: This study investigated the pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects.

Methods: This was an open-label, randomized, three-treatment, cross-over, clinical trial in healthy male subjects (n= 12) of known CYP2C9 and VKORC1 genotype who received a single oral dose of warfarin alone or after 2 weeks of pre-treatment with each herbal medicine at recommended doses. Pharmacodynamic (INR, platelet activity) and pharmacokinetic (warfarin enantiomer concentrations) end points were evaluated.

Results: The apparent clearance of (S)-warfarin (90% CI of ratio; 1.01, 1.18) was significantly higher during concomitant treatment with echinacea but this did not lead to a clinically significant change in INR (90% CI of AUC of INR; 0.91, 1.31). Policosanol did not significantly affect warfarin enantiomer pharmacokinetics or warfarin response. Neither echinacea nor policosanol had a significant effect on platelet aggregation after 2 weeks of pre-treatment with the respective herbal medicines.

Conclusion: Echinacea significantly reduced plasma concentrations of S-warfarin. However, neither echinacea nor policosanol significantly affected warfarin pharmacodynamics, platelet aggregation or baseline clotting status in healthy subjects.

Figure 1

Plasma concentration–time profile of (S)-warfarin after a single oral dose of warfarin either alone (solid squares) or after multiple doses of echinacea tablets (open squares) or policosanol tablets (open triangles). Values are presented as means ± SD

Figure 2

Plasma concentration–time profile of (R)-warfarin after a single oral dose of warfarin alone (solid squares) or after multiple doses of echinacea tablets (open squares) or policosanol tablets (open triangles). Values are presented as mean ± SD